Hypoglycemia Associated Autonomic Failure in Type 1 Diabetes Mellitus

NCT ID: NCT00607646

Last Updated: 2019-09-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2018-10-09

Brief Summary

Elevations of plasma cortisol, a stress hormone, during prior episodes of low blood sugar (hypoglycemia) appear to be responsible for the deficient responses during subsequent hypoglycemia. Our specific aim is to determine if dehydroepiandrosterone (DHEA), a hormone with anti-corticosteroid actions, can prevent hypoglycemia associated autonomic failure in type 1 diabetic volunteers.

Detailed Description

DHEA is the acronym for dehydroepiandrosterone, a steroid hormone produced naturally from cholesterol in the adrenal glands of males and females. It is also sold as an over-the-counter dietary supplement, and seems to have anticorticosteroid effects. DHEA antagonizes the effects of corticosterone on hippocampal function in rats and reduces responses to neural stress in mice. In our lab we have found that administration of the DHEA to rats during antecedent hypoglycemia, preserves counter-regulatory responses to subsequent hypoglycemia. The purpose of this study is to determine if the same response occurs in humans.

Conditions

Type 1 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: SINGLE

Study Groups

1

Hyperinsulinemic (high dose insulin) hypoglycemic clamp studies with oral administration of DHEA or placebo prior to each clamp x 2 on day 1. Day 2 hyperinsulinemic hypoglycemia. Participant randomized to either DHEA or placebo for baseline trial (arm 1) and 6 weeks treatment.

Group Type: EXPERIMENTAL

Dehydroepiandrosterone

Intervention Type: DRUG

Placebo tablets or tablets containing DHEA will be given orally before each hyperinsulinemic clamps on day 1 (x 2). Placebo tablets or tablets containing DHEA will be given orally before Day 2 hyperinsulinemic hypoglycemic clamp x 1.

2

Following 6 weeks randomized treatment, Day 1 hyperinsulinemic hypoglycemic clamps x 2 with DHEA or placebo dose given prior to each clamp. Day 2 hypoglycemia with prior dose of randomized treatment.

Group Type: EXPERIMENTAL

Dehydroepiandrosterone

Intervention Type: DRUG

Placebo tablets or tablets containing DHEA will be given orally before each hyperinsulinemic clamps on day 1 (x 2). Placebo tablets or tablets containing DHEA will be given orally before Day 2 hyperinsulinemic hypoglycemic clamp x 1.

Arm 3 (optional)

Individuals will be asked to return after at least 2 months and repeat the trial they did not complete (for example, placebo if they were in the DHEA trial before). Again Day 1 would consist of two hyperinsulinemic clamps with placebo or DHEA given orally. Day 2 hyperinsulinemic hypoglycemic clamp with oral administration of placebo or DHEA.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Placebo oral administration prior to each clamp period x2 on day 1. Hyperinsulinemic hypoglycemia on day 2.

Arm 4

Following 6 weeks randomized treatment, Day 1 hyperinsulinemic hypoglycemic clamps x 2 with DHEA or placebo dose given prior to each clamp. Day 2 hypoglycemia with prior dose of randomized treatment.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Placebo oral administration prior to each clamp period x2 on day 1. Hyperinsulinemic hypoglycemia on day 2.

Interventions

Dehydroepiandrosterone

Placebo tablets or tablets containing DHEA will be given orally before each hyperinsulinemic clamps on day 1 (x 2). Placebo tablets or tablets containing DHEA will be given orally before Day 2 hyperinsulinemic hypoglycemic clamp x 1.

Intervention Type: DRUG

Placebo

Placebo oral administration prior to each clamp period x2 on day 1. Hyperinsulinemic hypoglycemia on day 2.

Intervention Type: DRUG

Other Intervention Names

DHEA

Eligibility Criteria

Inclusion Criteria

• 28 (14 males, 14 females) Healthy volunteers aged 18-45 yr.
• 28 (14 males, 14 females) Type 1 diabetic patients aged 18-45 yr.
• HbA1c < 11.0%
• Has been diagnosed Type 1 DM
• No major diabetic tissue complications (i.e. history of retinopathy, neuropathy, stasis ulcers, etc)
• Body mass index < 40kg/m-2

Exclusion Criteria

• pregnancy

Medical history-

• Hepatic Failure/Jaundice
• Renal Failure
• Acute Cerebrovascular/ Neurological deficit

Physical Exam-

• Pneumonia
• Fever greater than 38.0 C
• Blood labs according to protocol

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Stephen N. Davis, MBBS

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stephen N. Davis, MD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Locations

University of Maryland, Baltimore

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

R01DK069803-03

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HP-00044672-DHEA

Identifier Type: -

Identifier Source: org_study_id